COPD is a progressive condition that leads to a pathological degeneration of the respiratory system. It represents one of the most important causes of mortality and morbidity in the world, and it is characterized by the presence of many associated comorbidities. Recent studies emphasize the thoracic area as one of the areas of the body concerned by the presence of pain with percentages between 22% and 54% in patients with COPD. This article analyzes the possible causes of mediastinal pain, including those less frequently taken into consideration, which concern the role of the fascial system of the mediastinum. The latter can be a source of pain especially when a chronic pathology is altering the structure of the connective tissue. We conclude that to consider the fascia in daily clinical activity may improve the therapeutic approach toward the patient.